RETREG1, also known as FAM134B, is a reticulophagy receptor crucial for regulating the turnover of the endoplasmic reticulum (ER) through selective phagocytosis. This process is integral to maintaining ER homeostasis, which is essential for normal cell function. RETREG1 is involved in the autophagy-related pathway, a key cellular process for degradation and recycling of cellular components [1].

Homozygous loss-of-function mutations in the RETREG1 gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features. Patients with these mutations show various degrees of motor signs along with sensory symptoms, such as muscle weakness, spasticity, and brisk tendon reflexes [2]. In addition, inhibition of RETREG1 contributes to impaired proteostasis in the ER due to the accumulation of misfolded or aggregated proteins, leading to compromised neuronal survival and progressive neuronal degenerative diseases [1].

In conclusion, RETREG1 is essential for maintaining ER homeostasis through its role in reticulophagy. Model-based research, especially studies on loss-of-function mutations in RETREG1, has revealed its significance in neuronal function and the development of neurodegenerative diseases. Understanding RETREG1 provides insights into the mechanisms underlying these diseases, potentially paving the way for new therapeutic strategies.

References:

1. Islam, Farhadul, Gopalan, Vinod, Lam, Alfred King-Yin. 2018. RETREG1 (FAM134B): A new player in human diseases: 15 years after the discovery in cancer. In Journal of cellular physiology, 233, 4479-4489. doi:10.1002/jcp.26384. https://pubmed.ncbi.nlm.nih.gov/29226326/

2. Çakar, Arman, Bagırova, Gulandam, Durmuş, Hacer, Uyguner, Oya, Parman, Yeşim. 2023. Phenotypic features of RETREG1-related hereditary sensory autonomic neuropathy. In Journal of the peripheral nervous system : JPNS, 28, 351-358. doi:10.1111/jns.12581. https://pubmed.ncbi.nlm.nih.gov/37448294/